Up-regulation of fast-axonally transported proteins in retinal ganglion cells of adult rats with optic-peroneal nerve grafts.
Metabolic labeling and quantitative 2D gel fluorography were used to assess changes in the synthesis and transport of five fast-axonally transported and developmentally regulated proteins (GAP-43, SNAP-25, and proteins of 18, 22, and 23/24 kDa) after grafting of a peroneal nerve segment onto a transected optic nerve in adult rats. After optic nerve transection alone, only GAP-43 was up-regulated significantly compared to normal adult controls. The other proteins showed little change or were down-regulated following axotomy. By 4 weeks following optic nerve transection and peroneal nerve grafting, however, GAP-43, proteins 22 and 23/24 kDa showed a sustained up-regulation in synthesis and transport compared to normal controls; SNAP-25 and protein 18 kDa showed levels of expression similar to or slightly greater than normal controls. Increased expression of GAP-43 in retinal ganglion cells was also examined with immunocytochemistry. While a transient up-regulation of GAP-43 in retinal ganglion cells was observed following optic nerve transection, a sustained increase in GAP-43 immunoreactivity was present only in animals with nerve grafts. Backfilling of retinal ganglion cells from the grafts with horseradish peroxidase combined with GAP-43 immunocytochemistry revealed that all retinal ganglion cells with axons growing into the grafts were positive for GAP-43, but not all retinal ganglion cells showing GAP-43 immunoreactivity were extending axons into the grafts. We conclude that the presence of a nerve graft sustains the up-regulation of a number of proteins including GAP-43, and that this up-regulation is correlated with an increased potential for nerve growth, but other as yet unknown factors or conditions appear to play a role in determining if this growth potential will be realized.
Wouters
B C
BC
Department of Cell Biology, Vanderbilt University School of Medicine, Medical Center North C-2310, Nashville, TN 37232, USA.
Bock-Samson
S
S
Little
K
K
Norden
J J
JJ
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001370:Axonal Transport; D001369:Axons / Q000502:physiology*; D019922:GAP-43 Protein / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D006735:Horseradish Peroxidase; D008297:Male; D008565:Membrane Proteins; D008970:Molecular Weight; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D009900:Optic Nerve / Q000502:physiology* / Q000601:surgery; D010543:Peroneal Nerve / Q000502:physiology* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25; D014184:Transplantation, Homologous
D019922:GAP-43 Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D006735:Horseradish Peroxidase